Alternative titles; symbols
HGNC Approved Gene Symbol: MIA
Cytogenetic location: 19q13.2 Genomic coordinates (GRCh38) : 19:40,775,160-40,777,490 (from NCBI)
Growth and expansion of tumor cells including malignant melanomas are modulated by a complex network of growth factors, which regulate proliferation and cell-matrix interaction through a variety of different signal transduction pathways. Blesch et al. (1994) purified a protein they called melanoma inhibitory activity (MIA) which is secreted by malignant melanoma cells and elicits growth inhibition of melanoma cells in vitro. Bosserhoff et al. (1996) cloned the gene encoding MIA and described its genomic organization. The gene encodes a 131-amino acid prepropolypeptide with a 24-residue secretion signal peptide sequence. The authors identified the transcription start site of the gene and studied the expression characteristics of the gene promoter in human melanoma, epithelial, and undifferentiated cells. Bosserhoff et al. (1996) found by Northern blot analysis that the MIA gene was expressed in all melanoma cell lines tested but was not expressed in fibroblast or epithelial cell lines.
Bosserhoff et al. (1996) determined that the MIA gene comprises 4 exons.
Bosserhoff et al. (1997) determined that MIA levels in patients with metastatic malignant melanoma were significantly above the 97th percentile level (6.5 ng/ml) determined for 72 normal controls. In a blinded, multicenter trial, Bosserhoff et al. (2000) analyzed serum MIA levels by ELISA in 259 patients with stage III and stage IV metastatic malignant melanoma. MIA levels were elevated in both groups and decreased significantly after surgery. MIA levels subsequently increased in 29 of 34 patients with rapid disease progression and decreased in 5 patients who responded to immunochemotherapy. Bosserhoff et al. (2000) suggested that MIA levels have prognostic value in staging and monitoring tumor load in malignant melanoma.
Crystal Structure
Lougheed et al. (2001) reported the crystal structure of human MIA. They stated that this was the first structural characterization of a secreted protein with an SH3 subdomain.
Koehler et al. (1996) mapped the MIA gene to chromosome 19q13.32-q13.33 by fluorescence in situ hybridization.
Blesch, A., Bosserhoff, A., Apfel, R., Behl, C., Hessdoerfer, B, Schmitt, A., Jachimczak, P., Lottspeich, F., Buettner, R., Bogdahn, U. Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA. Cancer Res. 54: 5695-5701, 1994. [PubMed: 7923218]
Bosserhoff, A. K., Hauschild, A., Hein, R., Schadendorf, D., Stockfleth, E., Bogenrieder, T., Landthaler, M., Buettner, R., Stolz, W. Elevated MIA serum levels are of relevance for management of metastasized malignant melanomas: results of a German multicenter study. J. Invest. Derm. 114: 395-396, 2000. [PubMed: 10722327] [Full Text: https://doi.org/10.1046/j.1523-1747.2000.00889.x]
Bosserhoff, A. K., Hein, R., Bogdahn, U., Buettner, R. Structure and promoter analysis of the gene encoding the human melanoma-inhibiting protein MIA. J. Biol. Chem. 271: 490-495, 1996. [PubMed: 8550608] [Full Text: https://doi.org/10.1074/jbc.271.1.490]
Bosserhoff, A. K., Kaufmann, M., Kaluza, B., Bartke, I., Zirngibl, H., Hein, R., Stolz, W., Buettner, R. Melanoma-inhibiting activity, a novel serum marker for progression of malignant melanoma. Cancer Res. 57: 3149-3153, 1997. [PubMed: 9242442]
Koehler, M. R., Bosserhoff, A.-K., von Beust, G., Bauer, A., Blesch, A., Buettner, R., Schlegel, J., Bogdahn, U., Schmid, M. Assignment of the human melanoma inhibitory activity gene (MIA) to 19q13.32-q13.33 by fluorescence in situ hybridization (FISH). Genomics 35: 265-267, 1996. [PubMed: 8661134] [Full Text: https://doi.org/10.1006/geno.1996.0352]
Lougheed, J. C., Holton, J. M., Alber, T., Bazan, J. F., Handel, T. M. Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins. Proc. Nat. Acad. Sci. 98: 5515-5520, 2001. [PubMed: 11331761] [Full Text: https://doi.org/10.1073/pnas.091601698]